PMID- 34295553
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220425
IS  - 2078-6891 (Print)
IS  - 2219-679X (Electronic)
IS  - 2078-6891 (Linking)
VI  - 12
IP  - 3
DP  - 2021 Jun
TI  - KRAS gene status in gastric signet-ring cell carcinoma patients and acts as 
      biomarker of MEK inhibitor.
PG  - 1020-1030
LID - 10.21037/jgo-20-617 [doi]
AB  - BACKGROUND: Signet-ring cell carcinoma (SRCC) is a specific subtype of stomach 
      cancer with unique epidemiology. Here, we sought to explore the role of KRAS in 
      SRCC. METHODS: KRAS status was studied both in The Cancer Genome Atlas (TCGA) and 
      internal cohorts. Immunohistochemistry (IHC) and fluorescence in situ 
      hybridization (FISH) were performed in formalin-fixed and paraffin-embedded 
      (FFPE) samples. We explored patients' survival and clinicopathological 
      characteristics in terms of KRAS mutation and expression. We also explored KRAS 
      status and drug response curve of MEK/mTOR inhibitors in SRCC cell lines. 
      RESULTS: Patients with KRAS mutations and copy number variation (CNV) showed 
      higher mRNA level compared to non-mutant cases (P=0.003 and P<0.001). In internal 
      cohort, 15 samples harbored KRAS mutations. Survival analysis showed that these 
      patients had significantly lower overall survival (OS) (P=0.048). We further 
      analyzed 75 patients with sufficient FFPE samples. Eight patients showed KRAS 
      mutations and one patient showed KRAS amplification. The median OS was 12.5 
      months for patients with KRAS mutation, and 19.5 months for patients without KRAS 
      mutation (P=0.005). Positive expression of KRAS as shown by IHC was detected in 
      majority of SRCC samples, which was higher than our intestinal cohort (28% vs. 
      12.6%, P=0.033). We further explored the correlation between KRAS status and drug 
      sensitivity in 4 SRCC cell lines. SNU601 and SNU668, which harbored KRAS 
      mutation, were hypersensitive to MEK and mTOR inhibitors than KRAS wide type cell 
      lines KATO-III and NUGC-4. CONCLUSIONS: Our findings demonstrate that KRAS gene 
      plays an important role in SRCC and reveals therapeutic potential of targeting 
      tumors by inhibiting MEK and mTOR pathways.
CI  - 2021 Journal of Gastrointestinal Oncology. All rights reserved.
FAU - Wu, Nandie
AU  - Wu N
AD  - The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing 
      University & Clinical Cancer Institute of Nanjing University, Nanjing, China.
FAU - Huang, Ying
AU  - Huang Y
AD  - The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing 
      University & Clinical Cancer Institute of Nanjing University, Nanjing, China.
FAU - Liu, Fangcen
AU  - Liu F
AD  - Department of Pathology, Drum Tower Hospital, Medical School of Nanjing 
      University, Nanjing, China.
FAU - Xu, Xingyun
AU  - Xu X
AD  - Department of Pathology, Drum Tower Hospital, Medical School of Nanjing 
      University, Nanjing, China.
FAU - Liu, Baorui
AU  - Liu B
AD  - The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing 
      University & Clinical Cancer Institute of Nanjing University, Nanjing, China.
FAU - Wei, Jia
AU  - Wei J
AD  - The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing 
      University & Clinical Cancer Institute of Nanjing University, Nanjing, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - J Gastrointest Oncol
JT  - Journal of gastrointestinal oncology
JID - 101557751
PMC - PMC8261324
OTO - NOTNLM
OT  - KRAS
OT  - amplification
OT  - gastric signet-ring cell carcinoma (SRCC)
OT  - point mutation
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at http://dx.doi.org/10.21037/jgo-20-617). The authors have no 
      conflicts of interest to declare.
EDAT- 2021/07/24 06:00
MHDA- 2021/07/24 06:01
PMCR- 2021/06/01
CRDT- 2021/07/23 06:49
PHST- 2020/12/27 00:00 [received]
PHST- 2021/03/28 00:00 [accepted]
PHST- 2021/07/23 06:49 [entrez]
PHST- 2021/07/24 06:00 [pubmed]
PHST- 2021/07/24 06:01 [medline]
PHST- 2021/06/01 00:00 [pmc-release]
AID - jgo-12-03-1020 [pii]
AID - 10.21037/jgo-20-617 [doi]
PST - ppublish
SO  - J Gastrointest Oncol. 2021 Jun;12(3):1020-1030. doi: 10.21037/jgo-20-617.